Low-frequency oscillations of finger skin blood flow during the initial stage of cold-induced vasodilation at different air temperatures.

BACKGROUND: Cold-induced vasodilation (CIVD) is known to be influenced by the ambient temperature. Frequency analysis of blood flow provides information on physiological regulation of the cardiovascular system, such as myogenic, neurogenic, endothelial nitric oxide (NO) dependent, and NO-independent activities. In this study, we hypothesized that the major origin of CIVD occurs prior to the CIVD event and investigated finger skin blood flow during the initial stage of CIVD at different ambient temperatures using frequency analysis. METHODS: Eighteen healthy volunteers immersed their fingers in 5 °C water at air temperatures of 20 °C and 25 °C. Finger skin blood flow was measured using laser Doppler flowmetry and analyzed using Morlet mother wavelet. We defined the time when the rate of blood flow increased dramatically as the onset of CIVD, and defined three phases as the periods from the onset of cooling to minimum blood flow (vasoconstriction), from minimum blood flow to the onset of CIVD (prior to CIVD), and from the onset of CIVD to maximum blood flow (CIVD). RESULTS: The increment ratio of blood flow at CIVD was significantly higher at 20 °C air temperature. In particular, at 20 °C air temperature, arteriovenous anastomoses (AVAs) might be closed at baseline, as finger skin temperature was much lower than at 25 °C air temperature, and endothelial NO-independent activity was significantly higher and neurogenic activity significantly lower during vasoconstriction than at baseline. Additionally, the differences in both activities between vasoconstriction and prior to CIVD were significant. On the other hand, there were no significant differences in endothelial NO-dependent activity between baseline and all phases at both air temperatures. CONCLUSIONS: Our results indicated that the increase of endothelial NO-independent activity and the decrease of neurogenic activity may contribute to the high increment ratio of blood flow at CIVD at 20 °C air temperature.

Diametric Comparison between the Thoracodorsal Vessel and Deep Inferior Epigastric Vessel in Breast Reconstruction.

BACKGROUND: In microvascular anastomosis, size discrepancy is common and can increase thrombotic complications. If size differences can be predicted, then vessels of the appropriate size can be selected. This study documented the difference in diameter between the thoracodorsal (TD) vessel and deep inferior epigastric perforator (DIEP) pedicle in each patient who underwent breast reconstruction using free tissue transfer. Patients and Methods. This retrospective study included 32 anastomoses (27 breasts including five cases of supercharged anastomosis) of breast reconstruction with the free DIEP flap and TD recipient between August 2018 and June 2019. In the microscopic view, the caliber of the TD vessel, the largest branch to the serratus anterior muscle, the descending branch, the largest and the second largest branches to the latissimus dorsi muscle, and the DIEP pedicle were measured. RESULTS: The diameter of the deep inferior epigastric artery was similar to that of the descending branch, and their anastomosing rate was 56.3%. The diameter of the deep inferior epigastric vein was similar to the branch to the serratus anterior muscle and the descending branch, and their anastomosing rates were 29.3% and 29.3%, respectively. All flaps were survived; however, in one case, a reoperation was needed to remove the hematoma, in which case fat necrosis occurred as the only complication. CONCLUSION: TD branches of similar size to the DIEP pedicle were prioritized in anastomosis. The descending branch and the branch to the serratus anterior muscle are expected to be good candidates as recipients in breast reconstruction with DIEP free flap. Moreover, supercharged anastomosis of DIEP pedicles can be achieved within TD branches.

Intermittent absent and reversed umbilical artery flows in appropriately grown monochorionic diamniotic twins in relation to proximate cord insertion: A harmful combination?

OBJECTIVE: To compare the prevalence of intermittent absent or reversed end-diastolic flow (iAREDF) in the umbilical artery in appropriately grown monochorionic diamniotic (MCDA) pregnancies with and without proximate cord insertion (PCI), and to evaluate pregnancy outcome. METHODS: The prevalence of iAREDF in MCDA pregnancies with PCI (n = 11) was compared with a control group without PCI (n = 33). PCI was defined as a distance between the cord insertions below the fifth percentile. Placental sharing, number, and diameter of anastomoses were assessed by placental examination. Pregnancy outcome was evaluated. RESULTS: iAREDF was present in 7/11 PCI pregnancies, compared with 0/33 in the control group (P ≤ .01). All PCI pregnancies and 94% of controls had arterioarterial (AA)-anastomoses (P = .56), the diameter was larger in the PCI group, respectively 3.3 vs 2.1 mm (P = .03). Three cases with iAREDF had adverse outcome, two resulted in fetal death of which one with brain damage in the co-twin, another underwent early premature emergency section for fetal distress. CONCLUSION: iAREDF occurs in a large proportion of MCDA pregnancies with PCI and is related to the diameter of the AA anastomosis. We hypothesize that iAREDF in appropriately grown MCDA twin pregnancies reflects an unstable hemodynamic balance with an increased risk for fetal deterioration. Whether outcome in these pregnancies can be improved by altered management requires further investigation.

The complex TIE between macrophages and angiogenesis.

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway.

Vascular access in children requiring maintenance haemodialysis: a consensus document by the European Society for Paediatric Nephrology Dialysis Working Group

There are three principle forms of vascular access available for the treatment of children with end stage kidney disease (ESKD) by haemodialysis: tunnelled catheters placed in a central vein (central venous lines, CVLs), arteriovenous fistulas (AVF), and arteriovenous grafts (AVG) using prosthetic orbiological material. Compared with the adult literature, there are few studies in children to provide evidence based guidelines for optimal vascular access type or its management and outcomes in children with ESKD.

Intra-pulmonary arteriovenous anastomoses and pulmonary gas exchange: evaluation by microspheres, contrast echocardiography and inert gas elimination.

KEY POINTS: Imaging techniques such as contrast echocardiography suggest that anatomical intra-pulmonary arteriovenous anastomoses (IPAVAs) are present at rest and are recruited to a greater extent in conditions such as exercise. IPAVAs have the potential to act as a shunt, although gas exchange methods have not demonstrated significant shunt in the normal lung. To evaluate this discrepancy, we compared anatomical shunt with 25-µm microspheres to contrast echocardiography, and gas exchange shunt measured by the multiple inert gas elimination technique (MIGET). Intra-pulmonary shunt measured by 25-µm microspheres was not significantly different from gas exchange shunt determined by MIGET, suggesting that MIGET does not underestimate the gas exchange consequences of anatomical shunt. A positive agitated saline contrast echocardiography score was associated with anatomical shunt measured by microspheres. Agitated saline contrast echocardiography had high sensitivity but low specificity to detect a ≥1% anatomical shunt, frequently detecting small shunts inconsequential for gas exchange. ABSTRACT: The echocardiographic visualization of transpulmonary agitated saline microbubbles suggests that anatomical intra-pulmonary arteriovenous anastomoses are recruited during exercise, in hypoxia, and when cardiac output is increased pharmacologically. However, the multiple inert gas elimination technique (MIGET) shows insignificant right-to-left gas exchange shunt in normal humans and canines. To evaluate this discrepancy, we measured anatomical shunt with 25-µm microspheres and compared the results to contrast echocardiography and MIGET-determined gas exchange shunt in nine anaesthetized, ventilated canines. Data were acquired under the following conditions: (1) at baseline, (2) 2 µg kg-1  min-1 i.v. dopamine, (3) 10 µg kg-1  min-1 i.v. dobutamine, and (4) following creation of an intra-atrial shunt (in four animals). Right to left anatomical shunt was quantified by the number of 25-µm microspheres recovered in systemic arterial blood. Ventilation-perfusion mismatch and gas exchange shunt were quantified by MIGET and cardiac output by direct Fick. Left ventricular contrast scores were assessed by agitated saline bubble counts, and separately by appearance of 25-µm microspheres. Across all conditions, anatomical shunt measured by 25-µm microspheres was not different from gas exchange shunt measured by MIGET (microspheres: 2.3 ± 7.4%; MIGET: 2.6 ± 6.1%, P = 0.64). Saline contrast bubble score was associated with microsphere shunt (ρ = 0.60, P < 0.001). Agitated saline contrast score had high sensitivity (100%) to detect a ≥1% shunt, but low specificity (22-48%). Gas exchange shunt by MIGET does not underestimate anatomical shunt measured using 25-µm microspheres. Contrast echocardiography is extremely sensitive, but not specific, often detecting small anatomical shunts which are inconsequential for gas exchange.

The protective effect of persistent trigeminal artery in patients with ischemic stroke.

BACKGROUND: Almost all case reports related to persistent trigeminal artery indicated that the existence of persistent trigeminal artery may increase the risk of ischemic stroke. However our case demonstrated that the persistent trigeminal artery may also play a protective role in preventing severe ischemic stroke by functioning as collateral circulation. CASE PRESENTATION: We reported a patient with left internal carotid artery occlusion with persistent trigeminal artery manifesting only as a minor acute ischemia stroke exhibiting acute onset of dizziness and difficulty in walking. Brain MRI showed two small areas of restricted diffusion on diffusion-weighted imaging in the left hemisphere. The digital subtraction angiography showed his left middle cerebral artery and bilateral anterior cerebral artery were supplied by the basilar artery via a persistent trigeminal artery. Furthermore, CT perfusion showed no remarkable difference between the two hemispheres. CONCLUSIONS: Persistent trigeminal artery may have a protective role in the setting of an acquired occlusion of homolateral internal carotid artery. Therefore, it is important to fully assess the presence of the persistent trigeminal artery in acute ischemic stroke.

Novel rodent model for simulation of sylvian fissure dissection and cerebrovascular bypass under subarachnoid hemorrhage conditions: technical note and timing study.

OBJECTIVESylvian fissure dissection following subarachnoid hemorrhage (SAH) is a challenging but fundamental skill in microneurosurgery, and one that has become increasingly difficult to develop during residency, given the overarching management trends. The authors describe a novel rodent model for simulation of sylvian fissure dissection and cerebrovascular bypass under SAH conditions.METHODSA standardized microvascular anastomosis model comprising rat femoral arteries and veins was used for the experimental framework. In the experimental protocol, following exposure and skeletonization of the vessels, extensive, superficial (1- to 2-mm) soft-tissue debridement was conducted and followed by wound closure and delayed reexploration at intervals of 7, 14, and 28 days. Two residents dissected 1 rat each per time point (n = 6 rats), completing vessel skeletonization followed by end-to-end artery/vein anastomoses. Videos were reviewed postprocedure to assess scar score and relative difficulty of dissection by blinded raters using 4-point Likert scales.RESULTSAt all time points, vessels were markedly invested in friable scar, and exposure was subjectively assessed as a reasonable surrogate for sylvian fissure dissection under SAH conditions. Scar score and relative difficulty of dissection both indicated 14 days as the most challenging time point.CONCLUSIONSThe authors' experimental model of femoral vessel skeletonization, circumferential superficial soft-tissue injury, and delayed reexploration provides a novel approximation of sylvian fissure dissection and cerebrovascular bypass under SAH conditions. The optimal reexploration interval appears to be 7-14 days. To the authors' knowledge, this is the first model of SAH simulation for microsurgical training, particularly in a live animal system.

Modified single pedicle reverse adipofascial flap for fingertip reconstruction.

BACKGROUND: Homodigital adipofascial flap is a well-established method for treating a distal fingertip defect; nonetheless, its use has some limitations. Reconstruction of fingertip injuries, with radial or ulnar tissue loss, may lead to some difficulties in providing an adequate bone coverage. The standard bipedicled technique did not allow the flap to cover the bone exposure without excessive tension. In our series, the reverse adipofascial flap had a single pedicle. The modified technique, because of its improved degree of rotation, granted the flap to reach either radial or ulnar tissue losses. PATIENTS AND METHODS: We treated 15 fingertip amputations distal to the lunula (9 Allen's type II and 6 type III), the mean size of defects was 2.7 cm2 (range, 1.8-3.2 cm2 ), the mean age of patients was 44 years (range, 22-63 years). Quick Disabilities of the Arm, Shoulder, and Hand score and Visual Analogue Scale were evaluated along with a 2-point discrimination test; the aesthetic satisfaction of the patients was estimated subjectively using a 5-point Likert scale. RESULTS: Mean flap size was 3.6 cm2 (range, 2.5-4.2 cm2 ), primary flap survival was observed in 14 out of 15 cases, partial flap necrosis was observed in 1 case, the nail grew in all fingers in about 6 months. Mean proximal and distal interphalangeal joint motion was 89° (range, 80°-100°) and 71° (range, 65°-80°), respectively. No complications were observed at the donor site. The median static 2-point discrimination was 4.5 mm (range, 3-8 mm), the mean quick DASH score was 2.6 (range, 0-9.1). All patients returned to work within a mean of 4.4 weeks (range, 4-5 weeks). The follow-up was 12 months. CONCLUSIONS: Single pedicle reverse adipofascial flap is an effective technique. This modified procedure allows a wider degree of flap rotation; it represents the ultimate arrow in our bow to address some particular defect geometry.

The use of arteriovenous anastomosis for venous drainage during Tamai zone I fingertip replantation.

PURPOSE: The purpose of this study was to evaluate outcomes for patients sustaining a distal fingertip amputation who underwent replantation witharteriovenous anastomosis for venous drainage over a one year period at our institution. This technique has been utilized when insufficient veins are identified in the amputated part for standard veno-venous anastomosis. METHODS: A retrospective study was performed on patients presenting from 2013 to 2014. Guillotine, crush, and avulsion/degloving injuries were included if they underwent fingertip (Tamai Zone I) replantation with arterial anastomosis for vascular inflow and arteriovenous anastomosis for venous drainage. The cases were further classified as Ishikawa subzone I and subzone II. RESULTS: Arteriovenous anastomosis for venous drainage during replantation was used in 45 digits in 35 patients. 41 of the 45 digits underwent successful replantation using this technique (91%). The mean active ROM in the DIP joint of the fingers and in the IP joint of thumbs was 65° and 57°, respectively. Sensory evaluation demonstrated a mean of 6.9 mm s2PD in digits where the digital nerves could be repaired. 11 replanted digits without nerve repair regained some sensory recovery with a mean of 9.6 mm s2PD. 91% of patients were highly satisfied with the appearance of the replanted digits based on Tamai criteria. CONCLUSIONS: Arteriovenous anastomosis for venous outflow should be considered during zone I fingertip replantation if sufficient veins are not identified in the amputated part. This technique may allow for more routine and successful distal replantation.

Relationship between quantitative and descriptive methods of studying blood flow through intrapulmonary arteriovenous anastomoses during exercise.

Several methods exist to study intrapulmonary arteriovenous anastomoses (IPAVA) in humans. Transthoracic saline contrast echocardiography (TTSCE), i.e., bubble scores, is minimally-invasive, but cannot be used to quantify the magnitude of blood flow through IPAVA (QIPAVA). Radiolabeled macroaggregates of albumin (99mTc-MAA) have been used to quantify QIPAVA in humans, but this requires injection of radioactive particles. Previous work has shown agreement between 99mTc-MAA and TTSCE, but this has not been tested simultaneously in the same group of subjects. Thus, the purpose of this study was to determine if there was a relationship between QIPAVA quantified with 99mTc-MAA and bubble scores obtained with TTSCE. To test this, we used 99mTc-MAA and TTSCE to quantify and detect QIPAVA at rest and during exercise in humans. QIPAVA significantly increased from rest to exercise using 99mTc-MAA and TTSCE and there was a moderately-strong, but significant relationship between methods. Our data suggest that high bubble scores generally correspond with large QIPAVA quantified with 99mTc-MAA during exercise.

Reduced blood flow through intrapulmonary arteriovenous anastomoses during exercise in lowlanders acclimatizing to high altitude.

NEW FINDINGS: What is the central question of this study? The aim was to determine, using the technique of agitated saline contrast echocardiography, whether exercise after 4-7 days at 5050 m would affect blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) compared with exercise at sea level. What is the main finding and its importance? Despite a significant increase in both cardiac output and pulmonary pressure during exercise at high altitude, there is very little Q̇IPAVA at rest or during exercise after 4-7 days of acclimatization. Mathematical modelling suggests that bubble instability at high altitude is an unlikely explanation for the reduced Q̇IPAVA. Blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) is elevated during exercise at sea level (SL) and at rest in acute normobaric hypoxia. After high altitude (HA) acclimatization, resting Q̇IPAVA is similar to that at SL, but it is unknown whether this is true during exercise at HA. We reasoned that exercise at HA (5050 m) would exacerbate Q̇IPAVA as a result of heightened pulmonary arterial pressure. Using a supine cycle ergometer, seven healthy adults free from intracardiac shunts underwent an incremental exercise test at SL [25, 50 and 75% of SL peak oxygen consumption (V̇O2 peak )] and at HA (25 and 50% of SL V̇O2 peak ). Echocardiography was used to determine cardiac output (Q̇) and pulmonary artery systolic pressure (PASP), and agitated saline contrast was used to determine Q̇IPAVA (bubble score; 0-5). The principal findings were as follows: (i) Q̇ was similar at SL rest (3.9 ± 0.47 l min-1 ) compared with HA rest (4.5 ± 0.49 l min-1 ; P = 0.382), but increased from rest during both SL and HA exercise (P < 0.001); (ii) PASP increased from SL rest (19.2 ± 0.7 mmHg) to HA rest (33.7 ± 2.8 mmHg; P = 0.001) and, compared with SL, PASP was further elevated during HA exercise (P = 0.003); (iii) Q̇IPAVA was increased from SL rest (0) to HA rest (median = 1; P = 0.04) and increased from resting values during SL exercise (P < 0.05), but was unchanged during HA exercise (P = 0.91), despite significant increases in Q̇ and PASP. Theoretical modelling of microbubble dissolution suggests that the lack of Q̇IPAVA in response to exercise at HA is unlikely to be caused by saline contrast instability.

Assessment of Pulmonary Capillary Blood Volume, Membrane Diffusing Capacity, and Intrapulmonary Arteriovenous Anastomoses During Exercise.

Exercise is a stress to the pulmonary vasculature. With incremental exercise, the pulmonary diffusing capacity (DLCO) must increase to meet the increased oxygen demand; otherwise, a diffusion limitation may occur. The increase in DLCO with exercise is due to increased capillary blood volume (Vc) and membrane diffusing capacity (Dm). Vc and Dm increase secondary to the recruitment and distension of pulmonary capillaries, increasing the surface area for gas exchange and decreasing pulmonary vascular resistance, thereby attenuating the increase in pulmonary arterial pressure. At the same time, the recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) during exercise may contribute to gas exchange impairment and/or prevent large increases in pulmonary artery pressure. We describe two techniques to evaluate pulmonary diffusion and circulation at rest and during exercise. The first technique uses multiple-fraction of inspired oxygen (FIO2) DLCO breath holds to determine Vc and Dm at rest and during exercise. Additionally, echocardiography with intravenous agitated saline contrast is used to assess IPAVAs recruitment. Representative data showed that the DLCO, Vc, and Dm increased with exercise intensity. Echocardiographic data showed no IPAVA recruitment at rest, while contrast bubbles were seen in the left ventricle with exercise, suggesting exercise-induced IPAVA recruitment. The evaluation of pulmonary capillary blood volume, membrane diffusing capacity, and IPAVA recruitment using echocardiographic methods is useful to characterize the ability of the lung vasculature to adapt to the stress of exercise in health as well as in diseased groups, such as those with pulmonary arterial hypertension and chronic obstructive pulmonary disease.

Cold-induced sympathetic tone modifies the impact of endothelium-dependent vasodilation in the finger pulp.

OBJECTIVE: In thermoneutral and cold subjects, the sympathetic nervous system regulates skin blood flow by adjusting frequency of the tonic vasoconstrictor impulses. However, the way these thermoregulatory impulses influence the vascular endothelium is not well known. We studied how the sympathetic nervous system influences endothelium-dependent vasodilation (EDV) caused by shear stress in skin containing arteriovenous anastomoses (AVAs) and arterioles in healthy subjects. METHODS: Thirteen healthy subjects were exposed to thermoneutral (29°C) and cold (22°C) ambient temperatures on separate days. EDV was induced by releasing suprasystolic pressure cuff applied to the forearm or third finger after 4min. Bilateral laser Doppler flux from the finger pulp, dorsal finger and dorsal wrist was measured together with ultrasound Doppler from the right radial artery. Absolute EDV response (EDV peak minus baseline) and normalized relative EDV response (ratio EDV peak/baseline) were calculated (median, 95% confidence interval). The relative EDV response reflect the size of EDV response independent of the baseline level and is thus used to compare the EDV responses in the finger pulp and wrist skin in the two temperature conditions. RESULTS: In finger pulp (dominated by AVAs), the absolute EDV response (flux, au) in thermoneutral (137.8 (67.5, 168.8)) and cold (130.3 (97.2, 154.9)) was the same (p=0.85), whereas the relative EDV response was significantly higher in cold (3.6 (2.5, 5.9)) than in thermoneutral (1.4 (1.1, 1.6), p=0.002). The same patterns were found in the radial artery. In the dorsal wrist (dominated by arterioles) the absolute EDV response (flux, au) was smaller in cold (30.9 (15.91, 38.0)) than in thermoneutral (52.1 (38.4, 57.8), p=0.04), whereas the relative EDV responses in cold (3.5 (2.3, 4.2)), and thermoneutral (2.3 (1.6, 2.7)) were equal (p=0.16). CONCLUSIONS: The relative EDV responses show that the impact of EDV on skin perfusion in cold conditions is significantly greater in the finger pulp than in wrist skin. However, the absolute EDV responses indicate that vascular smooth muscle relaxation during EDV is probably not affected by higher mild cold-induced sympathetic activity either in AVAs or in arterioles.

Arterio-venous anastomoses in isolated, perfused rat lungs.

Several studies have suggested that large-diameter (>25 µm) arterio-venous shunt pathways exist in the lungs of rats, dogs, and humans. We investigated the nature of these pathways by infusing specific-diameter fluorescent latex particles (4, 7, 15, 30, or 50 µm) into isolated, ventilated rat lungs perfused at constant pressure. All lungs received the same mass of latex (5 mg), which resulted in infused particle numbers that ranged from 1.7 × 107 4 µm particles to 7.5 × 104 50 µm particles. Particles were infused over 2 min. We used a flow cytometer to count particle appearances in venous effluent samples collected every 0.5 min for 12 min from the start of particle infusion. Cumulative percentages of infused particles that appeared in the samples averaged 3.17 ± 2.46% for 4 µm diameter particles, but ranged from 0.01% to 0.17% for larger particles. Appearances of 4 µm particles followed a rapid upslope beginning at 30 sec followed by a more gradual downslope that lasted for up to 12 min. All other particle diameters also began to appear at 30 sec, but followed highly irregular time courses. Infusion of 7 and 15 µm particles caused transient but significant perfusate flow reductions, while infusion of all other diameters caused insignificant reductions in flow. We conclude that small numbers of bypass vessels exist that can accommodate particle diameters of 7-to-50 µm. We further conclude that our 4 µm particle data are consistent with a well-developed network of serial and parallel perfusion pathways at the acinar level.

A methodological approach for quantifying and characterizing the stability of agitated saline contrast: implications for quantifying intrapulmonary shunt.

Agitated saline contrast echocardiography is often used to determine blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA). We applied indicator dilution theory to time-acoustic intensity curves obtained from a bolus injection of hand-agitated saline contrast to acquire a quantitative index of contrast mass. Using this methodology and an in vitro model of the pulmonary circulation, the purpose of this study was to determine the effect of transit time and gas composition [air vs. sulphur hexafluoride (SF6)] on contrast conservation between two detection sites separated by a convoluted network of vessels. We hypothesized that the contrast lost between the detection sites would increase with transit times and be reduced by using contrast bubbles composed of SF6 Changing the flow and/or reducing the volume of the circulatory network manipulated transit time. Contrast conservation was measured as the ratio of outflow and inflow contrast masses. For air, 53.2 ± 3.4% (SE) of contrast was conserved at a transit time of 9.25 ± 0.02 s but dropped to 16.0 ± 1.0% at a transit time of 10.17 ± 0.06 s. Compared with air, SF6 contrast conservation was significantly greater (P < 0.05) with 114.3 ± 2.9% and 73.7 ± 3.3% of contrast conserved at a transit time of 10.39 ± 0.02 s and 13.46 ± 0.04 s, respectively. In summary, time-acoustic intensity curves can quantify agitated saline contrast, but loss of contrast due to bubble dissolution makes measuring Q̇IPAVA across varying transit time difficult. Agitated saline composed of SF6 is stabilized and may be a suitable alternative for Q̇IPAVA measurement.

Dopamine receptor blockade improves pulmonary gas exchange but decreases exercise performance in healthy humans.

Pulmonary gas exchange, as evaluated by the alveolar-arterial oxygen difference (A-aDO2), is impaired during intense exercise, and has been correlated with recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) as measured by agitated saline contrast echocardiography. Previous work has shown that dopamine (DA) recruits IPAVA and increases venous admixture (Q̇s/Q̇t) at rest. As circulating DA increases during exercise, we hypothesized that A-aDO2 and IPAVA recruitment would be decreased with DA receptor blockade. Twelve healthy males (age: 25 ± 6 years, V̇O2 max : 58.6 ± 6.5 ml kg(-1) min(-1) ) performed two incremental staged cycling exercise sessions after ingestion of either placebo or a DA receptor blocker (metoclopramide 20 mg). Arterial blood gas, cardiorespiratory and IPAVA recruitment (evaluated by agitated saline contrast echocardiography) data were obtained at rest and during exercise up to 85% of V̇O2 max . On different days, participants also completed incremental exercise tests and exercise tolerance (time-to-exhaustion (TTE) at 85% of V̇O2 max ) with or without dopamine blockade. Compared to placebo, DA blockade did not change O2 consumption, CO2 production, or respiratory exchange ratio at any intensity. At 85% V̇O2 max , DA blockade decreased A-aDO2, increased arterial O2 saturation and minute ventilation, but did not reduce IPAVA recruitment, suggesting that positive saline contrast is unrelated to A-aDO2. Compared to placebo, DA blockade decreased maximal cardiac output, V̇O2 max and TTE. Despite improving pulmonary gas exchange, blocking dopamine receptors appears to be detrimental to exercise performance. These findings suggest that endogenous dopamine is important to the normal cardiopulmonary response to exercise and is necessary for optimal high-intensity exercise performance.

Endothelial cell dynamics during anastomosis in vitro.

Vascular anastomosis - the fusion of vessels from two distinct branches of the vascular system - represents a critical step in vascular growth under both healthy and pathological conditions, in vivo, and presents an important target for engineering of vascularized tissues, in vitro. Recent works in animal models have advanced our understanding of the molecular and cellular players in vascular anastomosis, but questions remain related to cellular dynamics and control of this process, in vitro. In this study, we exploited a three-dimensional (3-D) culture platform to examine the dynamics of endothelial cell (EC) during and after vascular anastomosis by allowing angiogenesis and vasculogenesis to proceed in parallel. We show that anastomosis occurs between sprouts formed by angiogenesis from an endothelium and tubes formed by vasculogenesis in the bulk of a 3-D matrix. This fusion leads to highly connected vessels that span from the surface of the matrix into the bulk in a manner that depends on cell density and identity. Further, we observe and analyze intermixing of endothelial cells of distinct origin (surface versus bulk) within the vessels structures that are formed; we provide evidence that the cells migrate along pre-existing vessels segments as part of this intermixing process. We conclude that anastomosis can occur between vessels emerging by angiogenesis and vasculogenesis and that this process may play an important role in contexts such as wound healing.

Intrapulmonary arteriovenous anastomoses in humans--response to exercise and the environment.

Intrapulmonary arteriovenous anastomoses (IPAVA) have been known to exist in human lungs for over 60 years. The majority of the work in this area has largely focused on characterizing the conditions in which IPAVA blood flow (Q̇IPAVA ) is either increased, e.g. during exercise, acute normobaric hypoxia, and the intravenous infusion of catecholamines, or absent/decreased, e.g. at rest and in all conditions with alveolar hyperoxia (FIO2 = 1.0). Additionally, Q̇IPAVA is present in utero and shortly after birth, but is reduced in older (>50 years) adults during exercise and with alveolar hypoxia, suggesting potential developmental origins and an effect of age. The physiological and pathophysiological roles of Q̇IPAVA are only beginning to be understood and therefore these data remain controversial. Although evidence is accumulating in support of important roles in both health and disease, including associations with pulmonary arterial pressure, and adverse neurological sequelae, there is much work that remains to be done to fully understand the physiological and pathophysiological roles of IPAVA. The development of novel approaches to studying these pathways that can overcome the limitations of the currently employed techniques will greatly help to better quantify Q̇IPAVA and identify the consequences of Q̇IPAVA on physiological and pathophysiological processes. Nevertheless, based on currently published data, our proposed working model is that Q̇IPAVA occurs due to passive recruitment under conditions of exercise and supine body posture, but can be further modified by active redistribution of pulmonary blood flow under hypoxic and hyperoxic conditions.